Title: Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation
Authors: Bohne, Felix ×
Martinez-Llordella, Marc
Lozano, Juan-Jose
Miguel, Rosa
Benitez, Carlos
Londono, Maria-Carlota
Manzia, Tommaso-Maria
Angelico, Roberta
Swinkels, Dorine W
Tjalsma, Harold
Lopez, Marta
Abraldes, Juan G
Bonaccorsi-Riani, Eliano
Jaeckel, Elmar
Taubert, Richard
Pirenne, Jacques
Rimola, Antoni
Tisone, Giuseppe
Sanchez-Fueyo, Alberto #
Issue Date: Jan-2012
Publisher: American Society for Clinical Investigation
Series Title: Journal of Clinical Investigation vol:122 issue:1 pages:368-382
Abstract: Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with non-tolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation.
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Abdominal Transplantation
Laboratory of Nephrology
× corresponding author
# (joint) last author

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